Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic review and meta-analysis.

Background: Despite clopidogrel therapy, patients undergoing percutaneous coronary intervention (PCI) with stenting are at risk of recurrent coronary events. This could be partly explained by a reduced efficacy of clopidogrel to inhibit platelet aggregation, an ex vivo defined phenomenon called clopidogrel nonresponsiveness or resistance. However, both prevalence and associated cardiovascular risks remain unclear. We systematically reviewed evidence on prevalence and clinical consequences of laboratory clopidogrel nonresponsiveness in patients undergoing PCI.

Methods: Using predefined strategies, we searched electronic databases. To be included, articles should report on PCI patients treated with clopidogrel, contain a clear description of the method used to establish the effects of clopidogrel, and report the prevalence of clopidogrel nonresponsiveness or incidence of cardiovascular events. We analyzed prevalences with a linear mixed model that accounts for study covariates and we pooled odds ratios of clinical consequences with a random-effects model.

Results: We identified 25 eligible studies that included a total of 3688 patients. Mean prevalence of clopidogrel nonresponsiveness was 21% (95% CI, 17%-25%) and was inversely correlated with time between clopidogrel loading and determination of nonresponsiveness and used loading dose. The pooled odds ratio of cardiovascular outcome was 8.0 (95% CI, 3.4-19.0).

Conclusions: Laboratory clopidogrel nonresponsiveness can be found in approximately 1 in 5 patients undergoing PCI. Patients ex vivo labeled nonresponsive are likely to be also "clinically nonresponsive," as they exhibit increased risks of worsened cardiovascular outcomes. Our results indicate that use of a 600-mg clopidogrel loading dose will reduce these risks, which needs to be confirmed in large prospective studies.